In Japan, the number of patients with pancreatic cancer has tended to increase year by year, and the number of deaths from pancreatic cancer was about 20,000 in 2001. Pancreatic cancer is ranked fifth among cancer deaths in men, and sixth among cancer deaths in women. Pancreatic cancer has poor prognosis, and the five-year survival rate of resected cases is 5 to 20%. Poor prognosis of pancreatic cancer is due to the fact that, in many cases, even a small cancer lesion (about 2 cm) invades organs outside of the pancreas, and metastasizes to the liver. Therefore, early diagnosis is very important for pancreatic cancer. However, there has not yet been provided a method for diagnosing pancreatic cancer before invasion thereof into organs surrounding the pancreas.
According to a nation-wide survey in Japan, the greatest number of pancreatic cancer cases is first detected through CT (44%), followed by ultrasonography (41%). Therefore, these two examination techniques are currently important for the diagnosis of pancreatic cancer. However, in the case of CT, which presently widely employed, cancer tissue and non-cancerous tissue are difficult to differentiate from each other, and diagnosis requires skilled experts. Examples of tumor markers for pancreatic cancer include CA19-9, DUPAN-2, Span-1, and CEA. Any of these markers shows positive in advanced cancer, but is not useful for early diagnosis of cancer, due to its low probability for diagnosis of early cancer. Furthermore, it has been known that CA19-9 is not suitable for use in diagnosis of pancreatic cancer, since blood CA19-9 level increases in the case of nonmalignancies (e.g., hepatitis, cirrhosis, or pancreatitis).
FDG-PET is also used for diagnosis of pancreatic cancer, but poses problems in terms of, for example, high examination cost and poor image resolution. Therefore, in view of the cost-effectiveness and performance of PET examination, demand has arisen for development of a probe which specifically recognizes pancreatic cancer tissue, as well as a method for diagnosing pancreatic cancer with high accuracy.
Pancreatic cancer is treated through surgery, chemotherapy, or radiotherapy. Among all pancreatic cancer cases, resectable cases account for 40% or less. In addition, the postoperative five-year survival rate is very low (5 to 20%). In the case of pancreatic cancer, surgery often causes problematic complications. Most pancreatic cancer cases detected through local progress or distant metastasis are not treated with surgery, but are treated with chemotherapy or radiotherapy. In recent years, pancreatic cancer cases have been increasingly treated with radiotherapy, since radiotherapy imposes less burden on the gastrointestinal tract and can also be applied to outpatients.
In view of the foregoing, demand has arisen for a new marker for diagnosis of pancreatic cancer, which realizes convenient and accurate examination for pancreatic cancer. In addition, demand has arisen for development of non-invasive and effective therapeutic means for pancreatic cancer; i.e., a therapeutic drug which causes damage specifically to pancreatic cancer cells.
In recent years, there have been actively developed methods for diagnosing or treating cancer by targeting a protein which is expressed specifically in cancer cells; i.e., methods for diagnosing or treating cancer, which employ a sample such as blood or tissue, and which target a cell surface protein that is highly expressed in cancer cells but is less expressed or not expressed in normal tissue. Diagnostic or therapeutic drugs (e.g., Herceptin) have already been provided in the clinical setting, and have contributed to treatment of many cancer patients. Furthermore, demand has arisen for the development of a cancer-specific therapeutic drug in a broad range of cancers.
AMIGO2 is very similar to AMIGO1 and AMIGO3 (which belong to the same family as AMIGO2) in terms of number of amino acids, domain, and gene sequence homology. All of these AMIGO proteins are single-transmembrane proteins, and have a signal peptide. This suggests that AMIGO2 protein is a membrane protein and is possibly secreted into blood. AMIGO family proteins have a similar structure; specifically, each of the proteins has six extracellular leucine-rich repeats (LRRs) and has an LRR amino-terminal domain and an LRR carboxyl-terminal domain such that the six LRR domains are provided therebetween. Each AMIGO family protein also has an immunoglobulin domain in the vicinity of an extracellular transmembrane domain. As has been suggested, AMIGO family proteins are expressed in nerve tissue and function as cell adhesion molecules (Non-Patent Document 1).
Patent Documents 1 and 2 describe that the AMIGO2 gene is highly expressed in gastric cancer, thyroid cancer, breast cancer, uterine cancer, renal cancer, lung cancer, colon cancer, or brain tumor, and that there is no difference in expression level of the AMIGO2 gene between pancreatic cancer and normal tissue. These documents describe that, in Examples in which antibodies are used, AMIGO protein expression associated with differentiation and progress in the rat fetal brain is confirmed through immunostaining, immunoprecipitation, or western blotting, but do not specifically describe that an anti-AMIGO2 antibody can be used for diagnosis or treatment of cancer.    Non-Patent Document 1: J. Cell Biol. 2003 Mar. 17; 160 (69): 963-73    Patent Document 1: WO 2004/003165 pamphlet    Patent Document 2: WO 2004/055055 pamphlet